A Ternary Copper (II) Complex with 4-Fluorophenoxyacetic Acid Hydrazide in Combination with Antibiotics Exhibits Positive Synergistic Effect against <i>Salmonella</i> Typhimurium
Guilherme Paz Monteiro,
Roberta Torres de Melo,
Micaela Guidotti-Takeuchi,
Carolyne Ferreira Dumont,
Rosanne Aparecida Capanema Ribeiro,
Wendell Guerra,
Luana Munique Sousa Ramos,
Drielly Aparecida Paixão,
Fernanda Aparecida Longato dos Santos,
Dália dos Prazeres Rodrigues,
Peter Boleij,
Patrícia Giovana Hoepers,
Daise Aparecida Rossi
Affiliations
Guilherme Paz Monteiro
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Roberta Torres de Melo
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Micaela Guidotti-Takeuchi
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Carolyne Ferreira Dumont
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Rosanne Aparecida Capanema Ribeiro
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Wendell Guerra
Institute of Chemistry, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Luana Munique Sousa Ramos
Institute of Chemistry, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Drielly Aparecida Paixão
Institute of Chemistry, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Fernanda Aparecida Longato dos Santos
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Dália dos Prazeres Rodrigues
Laboratory of Enterobacteriaceae, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil
Peter Boleij
Check-Points B.V., 6709 PD Wageningen, The Netherlands
Patrícia Giovana Hoepers
Postgraduate Program in Veterinary Science, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Daise Aparecida Rossi
Laboratory of Molecular Epidemiology, Federal University of Uberlândia, Uberlândia 38402-018, Brazil
Salmonella spp. continues to figure prominently in world epidemiological registries as one of the leading causes of bacterial foodborne disease. We characterised 43 Brazilian lineages of Salmonella Typhimurium (ST) strains, characterized drug resistance patterns, tested copper (II) complex as control options, and proposed effective antimicrobial measures. The minimum inhibitory concentration was evaluated for seven antimicrobials, isolated and combined with the copper (II) complex [Cu(4-FH)(phen)(ClO4)2] (4-FH = 4-fluorophenoxyacetic acid hydrazide and phen = 1,10-phenanthroline), known as DRI-12, in planktonic and sessile ST. In parallel, 42 resistance genes were screened (PCR/microarray). All strains were multidrug resistant (MDR). Resistance to carbapenems and polymyxins (86 and 88%, respectively) have drawn attention to the emergence of the problem in Brazil, and resistance is observed also to CIP and CFT (42 and 67%, respectively), the drugs of choice in treatment. Resistance to beta-lactams was associated with the genes blaTEM/blaCTX-M in 39% of the strains. Lower concentrations of DRI-12 (62.7 mg/L, or 100 μM) controlled planktonic and sessile ST in relation to AMP/SUL/TET and AMP/SUL/TET/COL, respectively. The synergistic effect provided by DRI-12 was significant for COL/CFT and COL/AMP in planktonic and sessile ST, respectively, and represents promising alternatives for the control of MDR ST.
